CLEVELAND – The White Sox looked ready to break their skid when they fell hard – again.
Carlos Santana hit a leadoff homer off Sox reliever Dylan Axelrod in the 10th inning, giving the streaking Cleveland Indians a 6-5 victory Wednesday night.
The Sox had taken a 5-3 lead in the ninth on a two-out, two-run single by Jeff Keppinger, but closer Addison Reed allowed two runs in the bottom of the frame to force extra innings.
Chicago, which has lost six in a row, fell 25 games below .500 for the first time since Sept. 11, 1989, at 40-65.
"None of us have the answer for what's going on," Reed said. "It's puzzling. I wish I knew how to fix it and get us out of this. When things are going bad, things are going bad."
Indians closer Chris Perez (4-1) tossed a scoreless 10th for the victory, while Axelrod (3-7) took the loss when Santana hit his 3-2 pitch over the right field fence.
It was Cleveland's seventh straight win – both overall and against the Sox – and its second walk-off victory in three days. On Monday, Jason Giambi belted a ninth-inning, pinch-hit homer off Ramon Troncoso to give the Indians a 3-2 triumph.
"(Cleveland) just kind of has that edge that you like to see in a team right now," Sox manager Robin Ventura said. "I was happy with the way our guys battled back, and we got a big at-bat and hit by Kep, but Reeder just didn't get it done the way you'd like."
Sox left-hander Jose Quintana went five innings and allowed three runs on seven hits, but wound up with his major-league leading 14th no-decision. He struck out six and walked two in his 22nd start of the season, departing with the Indians leading 3-0.
Chicago tied the score in the sixth with three runs off Cleveland right-hander Corey Kluber. Alexei Ramirez doubled home Josh Phegley with one out, while Alex Rios and Adam Dunn followed with RBI singles.
Sox relievers Nate Jones and David Purcey tossed three hitless innings to keep the game deadlocked until the ninth, when Keppinger pinch hit with the bases loaded and two out.
Keppinger saw three straight balls from Indians reliever Cody Allen, then took two strikes before sending a liner up the middle that gave Chicago a 5-3 lead.
"I knew he couldn't walk me there, so I was waiting on his four-seam fastball," said Keppinger, who had been in a 3-for-31 slump. "I was ready for it, and I was able to get a good result."
Reed allowed the first three hitters he faced to reach base. He allowed a double by Michael Brantley, hit Giambi with a pitch, and mishandled a bunt by Drew Stubbs.
Michael Bourn and Jason Kipnis brought home runs with sacrifice flies before Reed struck out Asdrubal Cabrera to end the inning.
"This was 100 percent my fault tonight," said Reed, who blew his fifth save in 31 opportunities. "I definitely did not make things easy on myself, letting the first three guys on. Hitting Giambi and not fielding the bunt cleanly were not good. I felt great again out there, but things just aren't working out the way I wanted them to."
Ventura didn't disagree, saying, "Q (Quintana) threw all right, then Jones and Purcey got us to the point to really give us a shot. It would be nice if (Reed) was sharper."
Kluber, who pitched a career high 8 2-3 innings, retired 10 straight batters until Conor Gillaspie singled with two out in the ninth. Allen entered and surrendered a single to Dayan Viciedo and a walk to Gordon Beckham, setting the stage for Keppinger.
The Indians, however, had two more rabbits in their hat and wound up with their ninth walk-off win of the season, three of them against the White Sox.
"Winning and the way you're winning breeds confidence," Cleveland manager Terry Francona said. "I always think we have a chance."
The White Sox remained quiet as the trade deadline passed at 4 p.m. EDT Wednesday. On Tuesday, Chicago dealt right-hander Jake Peavy to Boston in a three-way trade and acquired outfielder Avisail Garcia from the Tigers. The White Sox also received three other minor leaguers from the Red Sox, and assigned Garcia to Triple-A Charlotte.
"I'm pretty confident we're going to see him for a number of at-bats here in Chicago before the season's out," general manager Rick Hahn said.
NOTES: The White Sox recalled OF Jordan Danks from Triple-A Charlotte for the third time this season. Danks is batting .135 with one homer and two RBIs in 32 games with Chicago, but said he "made some small adjustments here and there, so I feel very good now at the plate." ... Ventura said RHP Andre Rienzo will remain in the starting rotation in Peavy's former spot. Rienzo became the first Brazilian-born pitcher in major league history when he went seven innings Tuesday in Cleveland's 7-4 victory. Rienzo allowed three unearned runs and did not figure in the decision. ... White Sox 1B Adam Dunn has 431 home runs, tying him with Cal Ripken Jr. for 43rd place all-time. White Sox DH Paul Konerko sits 45th on the list with 429. ... Chicago is 1-9 in its current stretch of 14 straight games against American League Central Division opponents. ... Indians RHP Justin Masterson (12-7) takes on White Sox LHP Chris Sale (6-10) in the four-game series finale Thursday at 12:05 p.m.